1. Field of Invention
The present invention pertains to the field of Positron Emission Tomography (PET) imaging. More particularly, this invention is related to the use of PET imaging for the detection of Alzheimer's disease.
2. Description of the Related Art
Alzheimer's disease (AD) is one of several neurodegenerative diseases characterized clinically by progressive dementia. It is well known that diagnosis of AD typically relies on the demonstration of distinctive histopathologic changes in a biopsy specimen, or is determined at autopsy. Routinely practiced clinical diagnosis of AD remains largely a diagnosis of exclusion, relying on standardized tests of mental function to document dementia and a battery of various other tests to rule out alternative toxic, metabolic, or structural etiologies. A substantial body of evidence has accrued suggesting the utility of 18F-2-fluoro-2-deoxy-D -glucose (FDG) Positron Emission Tomography (PET) in the clinical diagnosis of AD. UCLA studies, for example, show that PET is 93% sensitive and 76% specific for detection of AD, as discussed by Silverman et al., “Positron Emission Tomography in Evaluation of Dementia,” JAMA, 286:2120-2127 (2001). This reduction of FDG uptake translates to lower intensity in the image with respect to areas in the brain affected by the dementia. Classification of a pattern of reduced uptake typically relies on visual cues in the scan image and on extensive clinical experience.
Many studies identify AD by the comparison of the brains of AD patients to brains of subjects without AD. This is discussed by Alexander G E, et al., “Longitudinal PET Evaluation of Cerebral Metabolic Declines in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies,” Am. J. Psychiatry, 159:738-745 (2002). As taught by Silverman, et al., scans of a brain affected by AD reflect a heterogeneously reduced uptake of FDG in certain areas, which indicates decreased metabolic activity. Characterization of this pattern of reduced uptake is central to the assessment of PET as a diagnostic method for AD, and is essential to its application in clinical practice.
Herholz, K et al., “Discrimination Between Alzheimer Dementia and Controls by Automated Analysis of Multicenter FDG PET,” NeuroImage, 17:302-316 (2002), demonstrated a voxel-based method that shows the reduction of the cerebral metabolic rate of glucose (CMRGlc) in Alzheimer's patients for a certain age group. In a further study, Herholz, K. et al., “Comparibility of FDG PET Studies in Probable Alzheimer's Disease,” The Journal of Nuclear Medicine, 34:1460-1466 (1993), compared FDG uptake in different patients with probable AD from three different centers.